Chemical kinetics of reactions in the unfrozen solution of ice

Some reactions are accelerated in ice compared to aqueous solution at higher temperatures. Accelerated reactions in ice take place mainly due to the freeze-concentration effect of solutes in an unfrozen solution at temperatures higher than the eutectic point of the solution. Pincock was the first to report an acceleration model for reactions in ice,1 which successfully simulated experimental results. We propose here a modified version of the model for reactions in ice. The new model includes the total molar change involved in reactions in ice. Furthermore, we explain why many reactions are not accelerated in ice. The acceleration of reactions can be observed in the cases of (i) second- or higher-order reactions, (ii) low concentrations, and (iii) reactions with a small activation energy. Reactions with a buffer solution or additives in order to adjust ion strength, zero- or first-order reactions, or reactions containing high reactant concentrations are not accelerated by freezing. We conclude that the acceleration of reactions in the unfrozen solution of ice is not an abnormal phenomenon.     

Paired Electrochemical Reactions and the On‐Site Generation of a Chemical Reagent

While the majority of reported paired electrochemical reactions involve carefully matched cathodic and anodic reactions, the precise matching of half reactions in an electrolysis cell is not generally necessary. During a constant current electrolysis almost any oxidation and reduction reaction can be paired, and in the presented work we capitalize on this observation by examining the coupling of anodic oxidation reactions with the production of hydrogen gas for use as a reagent in remote, Pd‐catalyzed hydrogenation and hydrogenolysis reactions. To this end, an alcohol oxidation, an oxidative condensation, intramolecular anodic olefin coupling reactions, an amide oxidation, and a mediated oxidation were all shown to be compatible with the generation and use of hydrogen gas at the cathode. This pairing of an electrolysis reaction with the production of a chemical reagent or substrate has the potential to greatly expand the use of more energy efficient paired electrochemical reactions.     

Advances in capillary electrophoretically mediated microanalysis: an update

This review, as a continuation of an earlier report, gives an overview of recent developments, over the period from 2003 until now, in the use of capillary electrophoretic techniques for the in-line study of enzymatic reactions, derivatization, and chemical reactions. The article is divided into two parts: (i) in-line enzymatic reactions and (ii) in-line derivatization and chemical reactions. The first part introduces electrophoretically mediated microanalysis (EMMA) and discusses and illustrates the different modes of EMMA. A literature overview on enzymatic reactions is provided. The second part starts with an introduction of the procedures and the nomenclature used in the area of in-line derivatization and chemical reactions based on EMMA. Reported derivatization and chemical reaction procedures are discussed and summarized.     

Building addressable libraries: site-selective use of Pd(0) catalysts on microelectrode arrays

Site-selective Pd(0)-catalyzed reactions have been developed to functionalize a microelectrode array. Heck, Suzuki, and allylation reactions have all been accomplished. The reactions are compatible with both 1K and 12K arrays and work best when a nonsugar porous reaction layer is used. Suzuki reactions are faster than the Heck reactions and thus require more careful control of the reactions in order to maintain confinement. The allylation reaction requires a different confining agent than the Heck and Suzuki reactions but can be accomplished nicely with quinone as an oxidant for Pd(0).     

Microwave-assisted C-C bond forming cross-coupling reactions: an overview

Among the fundamental transformations in the field of synthetic organic chemistry, transition-metal-catalyzed reactions provide some of the most attractive methodologies for the formation of C-C and C-heteroatom bonds. As a result, the application of these reactions has increased tremendously during the past decades and cross-coupling reactions became a standard tool for synthetic organic chemists. Furthermore, a tremendous upsurge in the development of new catalysts and ligands, as well as an increased understanding of the mechanisms, has contributed substantially to recent advances in the field. Traditionally, organic reactions are carried out by conductive heating with an external heat source (for example, an oil bath). However, the application of microwave irradiation is a steadily gaining field as an alternative heating mode since its dawn at the end of the last century. This tutorial review focuses on some of the recent developments in the field of cross-coupling reactions assisted by microwave irradiation.     

Phase-Transfer Catalyzed Two-Phase Reactions in Preparative Organic Chemistry

Quaternary ammonium and phosphonium salts catalyze reactions between substances located partly in an aqueous and partly in an organic phase. Use of such phase-transfer catalysts simplifies and accelerates numerous reactions traditionally conducted in nonaqueous media. These reactions include carbene reactions, nucleophilic substitutions, alkylations of ketones and nitriles, Wittig and Darzens reactions, formation of ethers and esters. Other reactions such as hydrolysis and oxidation can be accelerated.     

Transition metal-catalyzed cyclocarbonylation in organic synthesis

Cyclocarbonylation reactions proceed mainly by the coupling reactions of carbonylation components with cyclization components having an unsaturated π-electron bond, in the presence of transition metal compounds. The representative reactions are cyclocarbonylation of alkynes by carbon monoxide such as Pauson–Khand reactions, hetero Pauson–Khand reactions, cyclocarbonylation of alkynyl alcohols, cyclocarbonylation of alkynyl amines, cyclocarbonylative alkyne–alkyne coupling reactions, and reductive cyclocarbonylation of alkynes. The other reactions are cyclocarbonylation of alkenes by carbon monoxide such as alkene–alkene coupling reactions, cyclocarbonylation with aldehydes, ketones, amines or imines, cyclocarbonylation of alkenyl alcohols. Carbonylation via cyclometalation, carbonylative ring expansion reactions, cyclocarbonylation by aldehydes, carboxylic acids or carboxylic acid esters are also cyclocarbonylation reactions. These reactions are conveniently used for organic syntheses, especially, for the syntheses of pharmaceutical intermediates.     

Kinetics and thermodynamics of the exchange reactions of peroxy radicals with hydroperoxides

The enthalpies and equilibrium constants of the exchange reactions of peroxy radicals with hydroperoxides of various structures are calculated. The experimental data on the reactions of hydrogen atom abstraction by the peroxy radicals from the hydroperoxides are analyzed, and the kinetic parameters characterizing these reactions are calculated using the intersecting parabolas method. The activation energies and rate constants for nine reactions of H atom abstraction by a peroxy radical from the OOH group of a peroxide are calculated using the above parameters. The geometric parameters of the transition states for the reactions are calculated. The low triplet repulsion plays an important role in the fast occurrence of the reactions. The polar interaction in the transition state is manifested in the reactions of the peroxy radicals with hydroperoxides containing a polar group.     

Aminolysis of Y-substituted phenyl diphenylphosphinates and benzoates: effect of modification of electrophilic center from C=O to P=O

The effect of modification of the electrophilic center from C=O to P=O on reactivity and reaction mechanism has been investigated for aminolysis of Y-substituted phenyl diphenylphosphinates (1a-j) and benzoates (2a-i). The phosphinates 1a-j are less reactive than the benzoates 2a-i. The reactions of 2,4-dinitrophenyl diphenylphosphinate (1a) with alicyclic secondary amines resulted in a linear Br?nsted-type plot with a beta(nuc) value of 0.38, while the corresponding reactions of 2,4-dinitrophenyl benzoate (2a) yielded a curved Br?nsted-type plot. Similarly, a linear Br?nsted-type plot with a beta(lg) value of -0.66 was obtained for the reactions of 1a-j with piperidine, while the corresponding reactions of 2a-i gave a curved Br?nsted-type plot. The linear Br?nsted-type plots for the reactions of 1a-j have been taken as evidence for a concerted mechanism, while the curved Br?nsted-type plots for the reactions of 2a-i have been suggested to indicate a change in the rate-determining step of a stepwise mechanism. The Hammett plot for the reactions of 1b-j exhibited a poor correlation with sigma(-) constants (R(2) = 0.962) but slightly better correlation with sigma(o) (R(2) = 0.986). However, the Yukawa-Tsuno plot for the same reactions resulted in an excellent correlation (R(2) = 0.9993) with an r value of 0.30. The aminolysis of 1a-j has been suggested to proceed through a concerted mechanism with an early transition state on the basis of the small beta(nuc) and small r values.     

Direct and quantitative monitoring of catalytic organic reactions under heterogeneous conditions using direct analysis in real time mass spectrometry

This new method overcomes problems of conventional analytical methodologies such as light scattering and sampling reproducibility issues. We used this method for mechanistic studies of catalytic reactions under heterogeneous conditions. Direct-type hydroxymethylation reactions and Mukaiyama-type hydroxymethylation reactions both catalyzed by a scandium–bipyridine ligand complex under micellar conditions were employed as examples of heterogeneous reactions. For direct-type hydroxymethylation reactions, initial reaction rate assays revealed first-order dependency on both substrate and catalyst. On the other hand, Mukaiyama-type hydroxymethylation reactions showed first-order rate dependency on substrate, zero-order on catalyst and saturation kinetics on formaldehyde.

A direct and quantitative method for monitoring heterogeneous organic reactions has been developed by using direct analysis in real time mass spectrometry (DART-MS) with an isotope-labeled reaction product as an internal standard.     

Control of up to five stereocenters in a cascade reaction: synthesis of highly functionalized five-membered rings

Mukaiyama-Aldol and Prins reactions have been identified as highly efficient methods in C-C bond formation since they were discovered several decades ago. Since both reactions gave the same common intermediate, oxocarbonium, we intend to combine the two reactions into a domino process, which means the formation of multiple C-C bonds and stereogenic centers in one pot without isolation of any intermediates. We envisage that the domino reactions involving the Mukaiyama-Aldol reaction of silyl enol ether and acetal treated with Lewis acid (TiBr4) will produce an oxonium intermediate which upon trapping by an alkene functionality in an intramolecular Prins cyclization will generate the cyclopentyl ring system.     

The reactions of chlorine monofluoride with unsaturated compounds and the dehydrohalogenation of some of the derivatives

The reactions of chlorine monofluoride with benzene, toluene and nitrobenzene to give monochloro derivatives has been investigated and its addition reactions to various substituted olefins studied. The products from all these reactions are consistent with the participation of a chloronium ion as the reactive species, even in solvents of low dielectric constant. The chlorofluoro addition products formed from the olefins have been dehydrohalogenated and the mechanism of reactions discussed in terms of an E1 cb mechanism or paene-carbonium ion extreme.     

High-Throughput Diversification of Complex Bioactive Molecules by Accelerated Synthesis in Microdroplets

Late-stage diversification of drug molecules is an important strategy in drug discovery that can be facilitated by reaction screening using high-throughput experimentation. Here we present a rapid method for functionalizing bioactive molecules based on accelerated reactions in microdroplets. Reaction mixtures are nebulized at throughputs better than 1 reaction/second and the accelerated reactions occurring in the microdroplets are followed by desorption electrospray ionization mass spectrometry (DESI-MS). Because the accelerated reactions occur on the millisecond timescale, they allow an overall screening throughput of 1 Hz working at the low nanogram scale. Using this approach, an opioid agonist (PZM21) and an antagonist (naloxone) were diversified using three reactions important in medicinal chemistry: sulfur fluoride exchange (SuFEx) click reactions, imine formation reactions, and ene-type click reactions. Some 269 functionalized analogs of naloxone and PZM21 were generated and characterized by tandem mass spectrometry (MS/MS) after screening over 500 reactions.     

Magnetic control of chemical transformations: application for programmed electrocatalysis and surface patterning

Lateral translocation of electrocatalyst-modified magnetic particles was achieved upon application of an external magnetic field. Programmed electrocatalytic reactions at different electrodes or different areas of an electrode were performed. The spatially controlled electrocatalytic reactions were exemplified with NADH electrocatalytic oxidation and with bioelectrocatalytic electrode patterning. The method will be particularly useful for programmed electrochemical reactions at interdigitated electrodes.     

MNDO study of reaction paths: Hydroboration of carbonyl systems

The hydroboration reactions of acetaldehyde and acetone have been investigated by the MNDO method. The reactions have been shown to be twostep reactions involving an intermediate adduct. This adduct subsequently undergoes hydrogen rearrangement. The hydroboration reactions of acetaldehyde and acetone have been compared with the corresponding reaction of formaldehyde. The charge transfer effects accompanying these reactions have also been discussed.     

Magnetic control of chemical transformations: application for programmed electrocatalysis and surface patterning

Lateral translocation of electrocatalyst-modified magnetic particles was achieved upon application of an external magnetic field. Programmed electrocatalytic reactions at different electrodes or different areas of an electrode were performed. The spatially controlled electrocatalytic reactions were exemplified with NADH electrocatalytic oxidation and with bioelectrocatalytic electrode patterning. The method will be particularly useful for programmed electrochemical reactions at interdigitated electrodes.     

有机合成的新世纪――－有机合成近年进展鉴赏

本文简要介绍了2005年至今有机合成领域的进展,第一部份有机合成方法学的一些新进展中突出介绍了金属参与的有机合成反应、自由基介导的合成反应、"一个反应瓶"内的多步反应以及不对称反应四个方面;第二部份复杂天然产物全合成则以10个分子的为例介绍这方面的进展。     

Quantum mechanical predictions of the stereoselectivities of proline-catalyzed asymmetric intermolecular aldol reactions

Quantum mechanical calculations were employed to predict the ratio of four stereoisomeric products expected from two complex reactions involving the aldol reactions of cyclohexanone with benzaldehyde or with isobutyraldehyde catalyzed by (S)-proline. Experimental tests of these predictions provide an assessment of the state-of-the-art in quantum mechanical prediction of products of complex organic reactions in solution.     

Oxidative cyclization based on reversing the polarity of enol ethers and ketene dithioacetals. Construction of a tetrahydrofuran ring and application to the synthesis of (+)-nemorensic Acid

The utility of oxidative cyclization reactions for the construction of tetrahydrofuran rings has been examined. In these experiments, alcohol nucleophiles were found to be effective traps for radical cation intermediates generated from both enol ether and ketene dithioacetal groups. The reactivity of the alcohol trapping group appeared to lie between that of an enol ether and an allylsilane trapping group. The stereochemical outcome of cyclization reactions originating from the oxidation of an enol ether was found to be controlled by stereoelectronic factors. The utility of these cyclization reactions was illustrated with the synthesis of a key tetrahydrofuran building block for the synthesis of linalool oxide and rotundisine. Cyclization reactions triggered by the oxidation of a ketene dithioacetal led to far greater levels of stereoselectivity. The stereochemical outcome of these reactions was shown to arise from steric factors involving the larger ketene acetal group. The synthetic utility of cyclizations utilizing ketene dithioacetal derived radical cations was demonstrated by completing an asymmetric synthesis of (+)-nemorensic acid. Finally, the reactions were shown to be compatible with the use of an amide nucleophile and the direct formation of a lactone product.     

Silicon-Free SuFEx Reactions of Sulfonimidoyl Fluorides: Scope,Enantioselectivity, and Mechanism

SuFEx reactions, in which an S−F moiety reacts with a silyl-protected phenol, have been developed as powerful click reactions. In the current paper we open up the potential of SuFEx reactions as enantioselective reactions, analyze the role of Si and outline the mechanism of this reaction. As a result, fast, high-yielding, “Si-free” and enantiospecific SuFEx reactions of sulfonimidoyl fluorides have been developed, and their mechanism shown, by both experimental and theoretical methods, to yield chiral products.